The effectiveness of radiotherapy would be improved if radiosensitizing drugs were used which acted differentially in sensitizing cancer cells more than normal tissues. Recent studies of lucanthone (Miracil D), 1-diethylamino-ethylamino-4-methyl-10-thioxanthenone, a relatively non-toxic drug widely used in the treatment of schistosomisis, indicate that it radiosensitizes by inhibiting repair of radiation damage, localizes in certain neoplastic tissues more than in adjacent skin and muscle, and causes a substantial radiosensitization of mouse tumors with little or no sensitization of adjacent normal tissues. In addition, limited clinical results indicate that lucanthone halved the 50% regression time following radiotherapy for the two tumor types tested. The utility of this promising adjuvant in radiotherapy could be improved if the treatment parameters associated with its administration were optimized and if its apparent lack of serious radiotoxicity to normal tissues were more extensively tested. The objectives of the proposed research are: (1) to determine in preclinical studies the optimum timing and optimum radiation dose rate for effective use of the drug, lucanthone, as an adjuvant in radiation therapy, (2) to determine in mice the extent of any possible radiosensitization with lucanthone of several important dose limiting normal tissues, and (3) to adapt the optimizing conditions of these preclinical studies to define and carry out a pilot clinical study of lucanthone in combination with radiotherapy in treatment of certain types of human tumors. The results will define and perhaps demonstrate more nearly optimum treatment parameters for use of this promising radiosensitizing drug in radiation therapy.